Force and transmembrane potential recording from extremely short segments of frog ventricle strips has been combined with techniques for rapid exchange of extracellular composition. Voltage clamp experiments with this preparation have indicated that activation of contraction is mediated exclusively, or almost exclusively, by calcium influx into the cell, and that such an influx arises from driving forces in addition to purely electrodiffusional ones. A further test of the first conclusion involves a study of the positive inotropic effect (already reported) of caffeine on frog ventricle and, in particular, the evaluation of any possible role of voltage-dependent or calcium-dependent release of calcium from intracellular stores in the positive inotropic effect of caffeine.